Sorbonne University, INSERM, Association Institute of Myology, Center of Research in Myology, Paris, France.
Department of Pharmacology and Physiology, The George Washington University, Washington, DC, United States.
Front Immunol. 2020 Jun 10;11:1074. doi: 10.3389/fimmu.2020.01074. eCollection 2020.
The thymus, a primary lymphoid organ, provides a complex environment essential for the generation of the T-cell repertoire. Thymic alterations occur during life either in the context of thymic involution upon aging or the pathophysiological context of Myasthenia Gravis (MG). These changes involve complicated regulatory networks, in which microRNAs (miRNAs) are key players. Here, we analyzed the role of miRNAs in thymocyte maturation and differentiation sustained by thymic epithelial cells. We compared data from the literature regarding the role of mouse thymic miRNAs and original data obtained from a human thymic miRnome study. We identified a set of highly expressed miRNAs defined as ThymiRs and investigated miRNA expression in infants as compared to adults to determine those associated with human thymic involution. Thymic changes are also frequently observed in MG, an autoimmune disease which results in the production of anti-acetylcholine receptor (AChR) antibodies that lead to muscle weaknesses. Alterations such as thymoma in late-onset MG patients and hyperplasia with ectopic germinal centers (GCs) in early-onset (EOMG) patients are found. Thymic miRNA expression has been studied in AChR-MG patients both in thymoma-associated MG (TAMG) and EOMG, and their function through their mRNA targets investigated. Most of the dysregulated thymic miRNAs in EOMG are associated with GC development, such as miR-7, miR-24, miR-139, miR-143, miR-145, miR-146, miR-150, miR-452, miR-548 or thymic inflammation, such as miR-125b, miR-146, or miR-29. Understanding these pathways may provide therapeutic targets or biomarkers of disease manifestations.
胸腺是主要的淋巴器官，为 T 细胞库的产生提供了复杂的环境。胸腺在生命过程中会发生变化，要么是随着年龄的增长而发生胸腺萎缩，要么是在重症肌无力 (MG) 的病理生理情况下发生变化。这些变化涉及复杂的调控网络，其中 microRNAs (miRNAs) 是关键参与者。在这里，我们分析了 miRNAs 在胸腺上皮细胞维持的胸腺细胞成熟和分化中的作用。我们比较了文献中关于小鼠胸腺 miRNAs 作用的数据和从人类胸腺 miRNA 组研究中获得的原始数据。我们确定了一组高度表达的 miRNAs，称为 ThymiRs，并研究了婴儿与成人相比的 miRNA 表达，以确定与人类胸腺萎缩相关的 miRNA。MG 也是一种自身免疫性疾病，其结果是产生抗乙酰胆碱受体 (AChR) 抗体，导致肌肉无力，因此也经常观察到胸腺变化。在迟发性 MG 患者中，如胸腺瘤，在早发性 (EOMG) 患者中，出现过度增生和异位生发中心 (GC)。在 AChR-MG 患者中，已经研究了胸腺瘤相关 MG (TAMG) 和 EOMG 中胸腺瘤相关 miRNA 的表达，以及通过其 mRNA 靶标研究其功能。EOMG 中大多数失调的胸腺 miRNAs 与 GC 发育有关，如 miR-7、miR-24、miR-139、miR-143、miR-145、miR-146、miR-150、miR-452、miR-548 或与胸腺炎症有关，如 miR-125b、miR-146 或 miR-29。了解这些途径可能为疾病表现提供治疗靶点或生物标志物。
